February 22, 2007

RESEARCH NOTES

Running, basketball and other high-impact sports may lead to stronger bones as people age, according to a new study presented at the annual meeting of the American Academy of Orthopaedic Surgeons.

Measurements conducted on Senior Olympic Games athletes found that the bone mineral density (BMD) for those who participated in impact sports was significantly greater than athletes who competed in low-impact sports like swimming and cycling.

“While we know that exercise is vital as we get older, this study finds that the kind of exercise we choose can be just as important,” said Vonda Wright, lead author and assistant professor in the Department of Orthopaedic Surgery at the School of Medicine. “The findings show that a key to maintaining strong, healthy bones as we age is to engage in impact sports,” added Wright, who is an orthopaedic surgeon at the UPMC Center for Sports Medicine.

The study evaluated 298 athletes competing in the 2005 Senior Olympics in Pittsburgh. The athletes, ages 50 to 93, completed a health history questionnaire and underwent ultrasound to measure BMD.

After controlling for age, sex, obesity and osteoporosis medication, participation in high-impact sports was found to be a significant predictor of BMD.

“The costs associated with caring for people with osteoporosis and fractures caused by frail bones are rising as the population ages,” Wright concluded. “Our study implies that persistent participation in impact sports can positively influence bone health even in the oldest athletes.”

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Findings of Autism Genome Project released

Preliminary findings from the largest genome scan ever completed in the history of autism research have been published in Nature Genetics. Pitt researchers are among 120 scientists from 50 institutions in 19 nations who contributed to this landmark research endeavor through the Autism Genome Project. The AGP began in 2002 when researchers from around the world decided to come together and share samples, data and expertise to facilitate the identification of autism susceptibility genes.

The data represent the first phase of the effort, which was to assemble the largest collection of autism DNA and complete the whole genome linkage scan.

“This project represents a new beginning in autism research, and provides an invaluable resource to researchers worldwide,” said Bernie Devlin, a Pitt associate professor of psychiatry and human genetics and a corresponding author of the study. “We hope that access to the tools and information developed through this project will help researchers begin to unravel the causes of autism.”

The collaboration is funded by the National Institutes of Health and by Autism Speaks, a non-profit organization dedicated to increasing awareness of autism and raising money to fund autism research.

The consortium looked for genetic commonality in autistic individuals from almost 1,200 families and scanned these families’ DNA for copy number variations, or sub-microscopic genomic insertions and deletions that scientists believe might be involved with this and other common diseases.

The results implicate a previously unidentified region of chromosome 11 and neurexin 1, a member of a gene family believed to be important in contact and communication between neurons, among other regions and genes in the genome. The neurexin finding, in particular, highlights a special group of neurons, called glutamate neurons, and the genes affecting their development and function, suggesting they play a critical role in autism spectrum disorders.

The consortium believes the identification of susceptibility genes will provide insight into the basis of autism, offering a route to breakthroughs in diagnosis and new treatments for the condition.

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Pharmacy’s diabetes course gets additional funding

NovoNordisk has awarded $500,000 to the Pitt School of Pharmacy in support of the school’s DM Educate project, a comprehensive 12-module online diabetes management course that is available to faculty and students at schools of pharmacy throughout the country. This gift brings the total amount of NovoNordisk’s support for the creation and marketing of DM Educate to $1.1 million.

The course was made available to pharmacy schools in last July and, thus far, 66 schools have registered to use the course in the fall 2006 and spring 2007 semesters. Approximately 4,000 students are projected to participate in the course in the first year.

This latest funding from NovoNordisk will be used to offer DM Educate to additional pharmacy students and to provide practicing pharmacists who also are preceptors with access to the course.

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Strong anti-cancer molecule created

A Pitt research team has created a synthetic anti-cancer molecule that someday may offer an alternative to people whose cancer does not respond to available medication. The Journal of the American Chemical Society published the researchers’ account of developing the molecule, known as meayamycin, online Feb. 6 with the print version to come out next month. More testing is needed to perfect meayamycin, but the project’s lead investigator is optimistic that the molecule, which is more powerful than current cancer drugs, will yield an effective treatment when fully developed.

Meayamycin stops cancer cells from dividing, much like the drug paclitaxel (sold as Taxol), except that in lab tests meayamycin did the job in lower concentrations, said principal investigator Kazunori Koide, assistant professor of chemistry.

Meayamycin packed the same punch as doses of commonly used drugs, like Taxol, but was 10-100 times stronger, he said. People might then need less meayamycin to get the same effect of current treatment dosages, thus helping to rein in treatment costs and possibly produce fewer side effects, Koide said.

In addition, meayamycin does not attach itself to a patient’s DNA or the usual protein targets within cells as current cancer drugs do. Some cancer does not respond to these currently available treatments, he said; meayamycin may give patients another option.

“Cancer is a lot more complicated than most diseases,” Koide said. “There are hundreds of causes of cancer at the genetic level. It’s impossible for any single cancer drug to work in everyone. But if there are no options available when a treatment fails, a person is left with nothing.”

In tests, meayamycin successfully worked against breast and cervical cancer cells as well as those from multi-drug-resistant cancers, Koide said.

Meayamycin is based on a compound developed by a Japanese company to combat colon and lung cancer as well as leukemia. It most likely works against those cancers, too, since the differences between it and the Japanese parent molecule are subtle except for meayamycin’s greater potency, Koide said.

The creation of the molecule is the culmination of six years of work supported by the National Institutes of Health.

“All new therapies start with new compounds made or isolated by chemists,” Koide said. “The chemistry requires a lot of intellectual curiosity, patience and dedication, and that has worked out so far. We have the blueprint to go from here to the end.”

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Professor questions evolution’s molecular assumption

Pitt anthropology professor Jeffrey H. Schwartz is working to debunk a major tenet of Darwinian evolution. Schwartz believes that evolutionary changes occur suddenly as opposed to the Darwinian model of evolution, which is characterized by gradual and constant change.

Among other scientific observations, gaps in the fossil record could bolster Schwartz’s theory because, for Schwartz, there is no “missing link.”

In an examination that further challenges the Darwinian model, Schwartz and co-author Bruno Maresca, a professor of biochemistry at the University of Salerno, Italy, look at the history and development of what the writers dub the “molecular assumption” (MA) in the article “Do Molecular Clocks Run at All? A Critique of Molecular Systematics,” published in the Feb. 9 issue of Biological Theory.

Schwartz contemplates the fact that the scientific community has accepted the MA as a scientific truth.

“That always struck me as being a very odd thing that this model of constant change was never challenged,” he said. Schwartz has his own theories regarding evolution, which are backed by recent developments in molecular biology.

The MA became a veritable scientific theory when, in 1962, biochemists Emil Zuckerkandl and Linus Pauling demonstrated species’ similarity through utilizing immunological activity between the blood’s serum and a constructed anti-serum. Upon observing the intensity of the serum and anti-serum reactivity between human, gorilla, horse, chicken and fish blood, Zuckerkandl and Pauling deduced “special relatedness” — the more intense the reaction, the more closely related the species were supposed to be.

Fish blood was most dissimilar, so it was assumed that the fish line diverged long before the other species. Human and gorilla blood were the most similar, meaning the two species had the least amount of time to diverge. Ultimately, the Darwinian model of constant evolutionary change was imposed upon the static observation made by Zuckerkandl and Pauling.

Schwartz argues that the structure of the genome — the genetic material that controls an organism’s development — does not keep changing, based on the presence of stress proteins, also known as heat shock proteins, in each cell. Their main function is to eliminate the potential for cellular error and change. This regular cellular maintenance is what Schwartz says is behind his refutation of constant cellular change. “The biology of the cell seems to run contrary to the model people have in their heads,” says Schwartz. He contends that if molecules were changing constantly, it would threaten proper survival, and strange animals would be emerging rapidly all over the world. Consequentially, Schwartz argues that molecular change is brought about only by significant environmental stressors, such as rapid temperature change, severe dietary change or even physical crowding.

If an organism’s stress proteins are unable to cope with a significant change, the genomic structure can be modified. However, Schwartz notes, a mutation also can be recessive in an organism for many generations before it is displayed in its offspring. Whether or not the offspring survives is another matter. If it does in fact live, the presence of this genetically modified organism is not the product of gradual molecular change but a sudden display of the genetic mutation, which may have occurred many years prior, he says.

However, it is not only the current molecular theory that intrigues Schwartz, but the failure of the scientific community to question an idea that is more than 40 years old: “The history of organ life is indemonstrable; we cannot prove a whole lot in evolutionary biology, and our findings will always be hypothesis. There is one true evolutionary history of life, and whether we will actually ever know it is not likely. Most importantly, we have to think about questioning underlying assumptions, whether we are dealing with molecules or anything else,” said Schwartz.

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UPB prof to study Filipino domestic violence

A Pitt-Bradford nursing professor has been awarded a $13,000 grant to spend five weeks this summer with two students in the Philippines researching domestic violence.

Perla Ilagan, assistant professor of nursing and a native of the Philippines, received the research abroad program grant from Pitt’s University Center for International Studies.

Ilagan has conducted two preliminary studies in the Philippines on domestic violence. Those studies were funded by the National Institute of Nursing Research and the National Institutes of Health.

“The findings from both studies indicated that 58-60 percent of the women experienced some type of abuse from their husbands or partners,” Ilagan said.

The aim of her upcoming study is to obtain an in-depth understanding of the meaning of domestic violence from the perceptions of Filipino men and women.

“Investigating the meaning of domestic violence from the perceptions of Filipino men and women could add to the existing body of knowledge and provide the foundation for developing a culturally sensitive and relevant education and prevention program for Filipino men and women,” Ilagan said.